Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To improve the treatment of patients with colorectal cancer, efforts must be directed toward the identification of patients likely to respond to a specific therapy, those who will experience severe toxicities, and those who will benefit from chemotherapy in the adjuvant setting. In recent years, studies on a global scale have attempted to define subsets of biochemical markers that may predict response to treatment (evaluated through clinical response, toxicity, and time to disease progression), and prognostic markers, which are equally important in determining how aggressive the disease is (generally evaluated in terms of overall survival), and the likelihood of disease recurrence after surgery. The science of pharmacogenomics is emerging as a useful molecular tool to investigate the disparity in drug efficacy by analyzing variations such as genetic polymorphisms in drug targets, metabolizing enzymes, transporters, and influential receptors. Consequently, the identification of accurate and validated predictive and prognostic markers combined with an increasing arsenal of therapeutic agents will improve the clinician's ability to tailor effective therapy to the molecular profile of the patient while minimizing life-threatening toxicities. This paper describes markers under study in the setting of colorectal cancer, including loss of heterozygosity of 18q and microsatellite instability, polymorphisms in thymidylate synthase, IL-8, CXCR-2, vascular endothelial growth factor, epidermal growth factor and their receptors, and K-ras mutations.
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PMID:Individualization of therapy for colorectal cancer based on clinical and molecular parameters. 1934 48

Elevated homocysteine is a risk marker for several major human pathologies. Emerging evidence suggests that perturbations of folate/homocysteine metabolism can directly modify production of inflammatory mediators. Pemetrexed acts by inhibiting thymidylate synthetase (TYMS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). EA.hy 926 cells grown under low ("Lo") and high ("Hi") folate conditions were treated with pemetrexed. The concentrations of several intracellular folate derivatives were measured using LC-MRM/MS. Lo cells had lower total folate concentrations and a different distribution of the intracellular folate derivatives than Hi cells. Treatment with pemetrexed caused a decrease in individual folate analytes. Microarray analysis showed that several genes were significantly up or down-regulated in pemetrexed treated Lo cells. Several of the significantly up-regulated transcripts were inflammatory. Changes in transcript levels of selected targets, including C3, IL-8, and DHFR, were confirmed by quantitative RT-PCR. C3 and IL-8 transcript levels were increased in pemetrexed-treated Lo cells relative to Lo controls; DHFR transcript levels were decreased. In Lo cells, IL-8 and C3 protein concentrations were increased following pemetrexed treatment. Pemetrexed drug treatment was shown in this study to have effects that lead to an increase in pro-inflammatory mediators in Lo cells. No such changes were observed in Hi cells, suggesting that pemetrexed could not modify the inflammatory profile in the context of cellular folate sufficiency.
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PMID:Pemetrexed alters folate phenotype and inflammatory profile in EA.hy 926 cells grown under low-folate conditions. 2297 65